299928-38-4Relevant academic research and scientific papers
Identification of a Water-Soluble Indirubin Derivative as Potent Inhibitor of Insulin-like Growth Factor 1 Receptor through Structural Modification of the Parent Natural Molecule
Cheng, Xinlai,Merz, Karl-Heinz,Vatter, Sandra,Zeller, Jochen,Muehlbeyer, Stephan,Thommet, Andrea,Christ, Jochen,W?lfl, Stefan,Eisenbrand, Gerhard
, p. 4949 - 4962 (2017/06/28)
Indirubins have been identified as potent ATP-competitive protein kinase inhibitors. Structural modifications in the 5-and 3′-position have been extensively investigated, but the impact of substituents in 5′-position is not equally well-studied. Here, we report the synthesis of new indirubin 3′-and 5′-derivatives in the search of water-soluble indirubins by introducing basic centers. Antiproliferative activity of all compounds in tumor cells was evaluated along with kinase inhibition of selected compounds. The results show the 3′-position to tolerate large substituents without compromising activity, whereas bulk and rigid substituents in 5′-position appear unfavorable. Screening molecular targets of water-soluble 3′-oxime ethers revealed 6ha as preferential inhibitor of insulin-like growth factor 1 receptor (IGF-1R) in a panel of 22 protein kinases and in cells. Consistently, 6ha inhibited tumor cell growth in the NCI 60 cell line panel and induced apoptosis. The results indicate that the 5′-position provides limited space for chemical modifications and identify 6ha as a potent water-soluble indirubin-based IGF-1R inhibitor.
Process for manufacturing N-acyl derivatives of glycines α-substituted by radicals of aromatic nature and novel products thereof
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, (2008/06/13)
This is an improved process of manufacturing N-acyl derivatives of glycines α-substituted by radicals with an aromatic nature by condensation of the addition product of glyoxylic acid and an amide, with an aromatic compound. In a first stage, the reaction is carried out at low temperature, in a concentrated sulfuric medium, of an aliphatic nitrile of the formula R--C N in which R is a radical selected from the group of substituted and unsubstituted, saturated and unsaturated alkyl radicals, with a concentrated aqueous solution of glyoxylic acid. Then in a second stage, the mixture obtained is condensed also at low temperature with a compound of aromatic nature not including a hydroxyl group and having at least one substitutable free hydrogen, and the resulting product is collected. The concentrated sulfuric acid may be supplemented with acetic acid during the second stage. A surface active agent may be also added in this stage. The products are valuable intermediates for the preparation of semi-synthetic penicillins.
